Scale setting for Nf=3+1N_f=3+1 QCD

We present the scale setting for a new set of gauge configurations generated with $N_f=3+1$ Wilson quarks with a non-perturbatively determined clover coefficient in a massive O($a$) improvement scheme. The three light quarks are degenerate, with the sum of their masses being equal to its value in nature and the charm quark has its physical mass. We use open boundary conditions in time direction to avoid the problem of topological freezing at small lattice spacings and twisted-mass reweighting for improved stability of the simulations. The decoupling of charm at low energy allows us to set the scale by measuring the value of the low-energy quantity $t_0^\star/a^2$, which is the flow scale $t_0$ at our mass point, and comparing it to an $N_f=2+1$ result in physical units. We present the details of the algorithmic setup and tuning procedure and give the bare parameters of ensembles with two lattice spacings a=0.054 fm and a=0.043 fm. We discuss finite volume effects and lattice artifacts and present physical results for the charmonium spectrum. In particular the hyperfine splitting between the $\eta_c$ and $J/\psi$ mesons agrees very well with its physical value.Comment: 25 pages, 9 figures. Version accepted for publication in the European Physical Journal

ELISA.

<p>Optical density (OD) at 450 nm measured at 2.5 h of pNPP incubation. OD for the different compounds at different concentrations is given. A and B illustrate the ability of the compounds to recognize Aβ fibrils. They indicate two series of experiments performed with following compounds A: ACI-80-Kφ to ACI-86-Kφ. ACI-80 without φ-label was run as a control. B: ACI-87-Kφ to ACI-89-Kφ, as well as fluorinated derivatives. ACI-80-Kφ, ACI-82-Kφ and ACI-83-Kφ were included as controls. C and D illustrate the ability of the compounds to recognize peptide film which largely consists of Aβ monomers.</p

Pyroglutamate content of ACI-80, ACI-80-Kφ and [¹²⁷I]-ACI-80.

<p>Kφ presents a lysine (K) linked to a fluorescein isothiocyanate (φ).</p

List of investigated D-enantiomeric peptide compounds.

<p>Modifications in the original amino acid sequence of ACI-80 are printed in bold. Amino acid residues are given in the one-letter-code. All amino-acids are D-enantiomers. Kφ presents a lysine (K) linked to a fluorescein isothiocyanate (φ).</p

Results for compound – Aβ fibril interactions obtained with the heterogeneous ligand model.

<p>Results for compound – Aβ fibril interactions obtained with the heterogeneous ligand model.</p

ELISA: Mean binding values for compounds with concentration of 10 µg/ml.

<p>All values were compared to that of ACI-80-Kφ. Compound binding to compound film, containing predominantly monomers and to fibrils was measured. Average values of two or three experiments unless marked otherwise. *value of one single experiment only. Kφ presents a lysine (K) linked to a fluorescein isothiocyanate (φ).</p

Results of the binding assays for ACI-80-Kφ derivatives to Aβ1–42 fibrils using surface plasmon resonance.

<p>Interaction and dissociation was measured with respect to the maximal interaction signal during injection and the response 60 s after the end of injection, respectively. ACI-80-Kφ binding was defined as 100%. Kφ presents a lysine (K) linked to a fluorescein isothiocyanate (φ).</p

<i>Ex vivo</i> staining of brain tissue sections from 13 months old male double transgenic AD mice APP (V717I) x PS1 (A246E) using different φ-labeled ACI-80 derivatives, 6E10-Aβ-antibody and DAPI.

<p>Left column: triple image overlay of respective stains reveal that the φ-compounds identify plaques. White scale bars 20 µm. Results of non-transgenic litter mate controls are not shown as no staining of φ-labeled ACI-80 derivatives and 6E10-Aβ-antibody could be detected.</p

D-enantiomeric peptide variants binding to fibrillar Aß1–42, covalently immobilized on a CM5 sensor chip via amine coupling.

<p>For each peptide variant experimental sensorgrams (black traces) obtained with injections at 2500 nM, 12500 nM and 62500 nM (ACI-80-Kφ, ACI-87-Kφ) or 500 nM, 2500 nM and 12500 nM (ACI-88-Kφ, ACI-89-Kφ) are shown. Injections were performed for 60 seconds each and dissociation phases were recorded for at least 30 seconds. The sensorgrams were globally fit (red curves) to a heterogeneous ligand model accounting for different refractive indices.</p

Surface plasmon resonance analysis of the interaction between immobilized Aβ1–42 fibrils and ACI-80-Kφ and various derivatives (Kφ presents a lysine (K) covalently linked to a fluorescein isothiocyanate (φ).

<p>ACI-80 derivatives were solved in running buffer (PBS, pH 7.4). The injected volume of ACI-80 derivatives was 10 µl of a 50 µg/ml concentration using a flow rate of 5 µl/min. The response of ACI-80-Kφ in resonance units [RU] was defined as 100%. Values >100% denote increased Aβ interaction of the ACI-80 derivative in comparison to ACI-80-Kφ. All derivatives were φ-labeled. Only the variations in comparison to ACI-80-Kφ are indicated in the figure.</p